Food-borne polystyrene microplastic exposure exacerbates cognitive deficiency via enhanced neuronal synaptic damage and neuroinflammation in Alzheimer's disease

The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented, yet the potential role of PS-MPs exposure in exacerbating neuronal damage and neuroinflammation in Alzheimer's disease (AD) remains unclear. Our research demonstrated that oral exposure to PS-MPs caused hippocampal mitochondrial damage in APP/PS1 mice, reduced expression of hippocampal mitochondrial and synapse-associated proteins, inhibited ErbB4 signaling pathway, and damaged hippocampal neurons. Additionally, PS-MPs exposure induced overactivation of astrocytes and microglia with NLRP3 pathway activation, increased β-amyloid (Aβ) deposition, and ultimately worsened cognitive dysfunction in APP/PS1 mice. Subsequent in vitro findings showed that PS-MPs exacerbated hippocampal neuronal damage under Aβ pathology, suppressed ErbB4 signaling pathway, and disrupted mitochondrial and synaptic function. The compromised hippocampal neurons enhanced microglial NLRP3 pathway activation. These results suggest that exposure to PS-MPs induces hippocampal neuronal damage, impairs mitochondrial and synaptic function, and exacerbates neuroinflammation and cognitive deficits, ultimately contributing to AD progression. Collectively, these findings enhance our understanding of the mechanisms by which MPs expedite the progression and influence management of AD.